Infectious diseases are caused by a pathogenic microorganism, like a virus, bacterium, fungus, or the like which enters and propagates in a living body. Common strategies to treat infectious diseases include the administration of an antimicrobial drug (antiviral or antibiotic) to patients suffering from such infections.
In many of cases the pathogenic microorganisms are eradicated or subsided by the action of a chemotherapeutic agent. However, in cases involving infections induced by human immunodeficiency virus (HIV) or herpes virus, the causative agents are not easily eradicated, if at all. Microorganisms may also acquire resistance to drugs. Furthermore, chemotherapeutic agents are generally toxic to varying degrees to patients. For example, an anti-HIV drug, AZT, causes life-threatening toxicity and anemia in about 70% of treated patients. Prolonged treatment results almost invariably in emergence of drug-resistant HIV. As a result, known antibiotics and antivirals have not been entirely satisfactory in terms of their antimicrobial spectrum, antimicrobial activity, behavior in the body, safety, or ability to induce the appearance of drug-resistant microorganisms.
Alternatives to chemotherapy include immunotherapeutic treatment, such as a vaccination. Administration of vaccines to non-infected hosts is referred to as “preventive vaccinating” while administration to already infected hosts has been referred to as “therapeutic vaccination.” The term “prevention” includes an attempt to halt the occurrence of a disease or disorder before it happens. The term “therapy” includes an attempt to alleviate the disease or clinical condition of an afflicted subject. The term “immunotherapeutic” includes an attempt to activate or modulate the immune system of the host. The term “subject” or “host” as used hereinafter generally means humans. However, other animal species are equally regarded as suitable hosts or subjects such as for example primates, horses, cows, pigs, sheep, goats, dogs, cats, rodents, fowl, fish, shellfish, crustaceans, worms, etc.
Vaccines usually come in injectable forms and are thus problematic for a widespread use, requiring specialized skills for delivery. As of today very few oral vaccines are known. An example of an oral vaccine is Sabin's attenuated polio vaccine which contains live but less virulent virus. The effect of such oral vaccines is less predictable due to the destructive nature of the digestive milieu and potential danger of virus being reverted to virulent form. It is recognized that on passage to the stomach, the vaccine antigenic component(s) are rapidly inactivated by the gastric pH and digestive enzymes, and thus systemic assimilation through the gut wall is poor or non-existent.
Thus, there remains a long-felt need for better therapies or a vaccine, which preserves its activity despite hostile environment in the stomach and intestines. Such therapies are additionally needs to be free of undesirable properties, such as patient toxicity or even death, the inducement of drug resistance, and the requirement of complicated routes or means of delivery.
The body of a living organism is composed of unit(s) generally known as a “cell.” Cells assemble in the body to form what is known as a “tissue.” Blood is considered a specialized form of connective tissue being a part of the hematopoietic system. Processed blood products, such as dried deer blood, have been described as an alleged health-invigorating food supplement. See, for example, U.S. Pat. No. 5,637,345 incorporated by reference herein. Whatever its eventual use it is imperative that products be obtained from blood of healthy donors and not from sick or infected donors. Wary of causing or spreading infection, pathogen-contaminated blood or tissue is generally discarded as unsuitable for any use.
Modern vaccines are mostly “acellular” or “subunit” vaccines in which the immunogen is composed of a single bacterial/viral protein or fragment thereof. In some vaccines the immunogen is a nucleic acid of the pathogen or modified or unmodified pathogen itself.
The overwhelming majority of vaccines are administered by injection because it is generally believed that oral administration of a vaccine leads to its destruction in the digestive tract. Nevertheless, the search of the U.S. PTO database for patents containing in their claims keywords such as “vaccine” and “virus” and “oral” results in about 40 patents. The review of such patents reveals that almost every one of them teaches chemically or physically modified forms of the antigen or immunogen, mainly aimed to prevent their degradation in the stomach and gut. Commonly these modifications include entrapment in indigestible polymeric carriers, e.g., U.S. Pat. No. 6,096,291; co-administration of acid neutralizing buffers, e.g., U.S. Pat. No. 5,932,223; co-administration of oil emulsions U.S. Pat. No. 5,885,590; co-administration of absorption enhancing compounds, e.g., U.S. Pat. No. 5,653,987; orally-administered package that will only dissolve in the host animal's gut, e.g., U.S. Pat. No. 5,676,950; and other complicated and time-consuming safeguarding efforts. Other approaches include expression of foreign, animal antigen (usually a single protein) in genetically modified transgenic plants and oral administration of the recombinant antigen in form of an edible plant, e.g., U.S. Pat. No. 5,889,189. However, in these plants such antigens are not naturally occurring since by definition the animal pathogen cannot infect vegetable tissues. Similarly, U.S. Pat. No. 5,643,577 discloses an oral vaccine comprising an influenza antigen associated with red blood cells. Here again this virus is not natural to the host cell since influenza virus is not capable of infecting red blood cells. Thus, none of the known strategies teaches, discloses, or suggests a composition comprising a pathogen or a plurality of antigens of a pathogen and pathogen-infected tissue, e.g., infected blood, of an animal.
The present inventor describes a simple vaccine comprising a pathogenic antigen and pathogen-infected host tissue. The composition of the invention overcomes the difficulties inherent in prior delivery systems and serves to introduce health modifying agents into and across the mucosal membrane of a human or animal subject. The composition of the invention is administered through a mucosal surface, e.g., enterally by an oral route, to provide significant clinical benefit to infected subjects. In a preferred embodiment, the vaccine is not subjected to any special modification aimed at enhancing the antigen “survival” in a hostile digestive milieu.
The innovative vaccine provides protection both by whole body immunity as well as in the critically important mucosal tissues, such as the cervix, uterus, and rectum where a pathogen often first enters the body during sexual contact or other transmucosal means into person to be infected. Because the gastrointestinal mucosa is a vast interface between the body and the environment, it is the main entry site for many antigens. In tests on animals and patients, the vaccines induces strong reactions by mucosal immune cells in the time frame required to stop infection. At the same time, the vaccines also stimulate strong humoral and cell-mediated reactions to fight pathogen in the blood stream. Thus, as oral vaccines, they work right away on the mucosal cells, then stimulate or down-modulate systemic immunity by raising antibody responses and priming killer cells.
The present invention provides a surprisingly effective and broadly applicable strategy for treating and preventing a variety of microbial infections in diverse host organisms ranging from humans to insects. The same composition is remarkably effective in treating cancer and immune disorders of autoimmune and inflammatory nature.